Method for Manufacture of Carboxyalkylinulin

ABSTRACT

A method for the manufacture of carboxyalkylinulin is disclosed comprising preparing an aqueous medium containing dispersed therein a halogenoalkylcarboxylate, adding to the carboxylate containing medium, under substantially neutral pH conditions, an inulin followed by heating this mixture to a temperature in the range of from 60° C. to 90° C. and proceeding with the reaction at alkaline conditions, pH 8-12, while simultaneously adding additional halogenoalkylcarboxylate and alkalihydroxide. The carboxyalkylinulin so formed is recovered in a manner known per sé.

This invention relates to a method for the manufacture ofcarboxyalkylinulin by reacting inulin with monochlorocarboxylic acidunder predominantly alkaline conditions. The inventive arrangementamounts to a multi-step process comprising dispersing into an aqueousmedium from about 25 to about 150 molar-% of thehalogenoalkylcarboxylate, expressed in relation to the molar amount ofmonosaccharide units in the inulin, followed by adding the inulin to thehalogenoalkylcarboxylate medium to thus yield a slurry, having a pH inthe range of from 5 to 8 , containing from about 25% to about 70% ofinulin, expressed in relation to the amount of water (100%) in theslurry. The slurry so obtained is thereafter heated to a temperaturefrom about 60° C. to about 90° C., followed by concurrently addingfurther halogenoalkylcarboxylate to yield a molar ratio ofhalogenoalkylcarboxylate:inulin of from 1.0 to 5.0, and an alkalinehydroxide in a quantity equimolar to the total level ofhalogenoalkylcarboxylate, plus an additional amount of the alkalinehydroxide of from 10 to 50 molar-%, expressed in relation to the molaramount of monosaccharide units in the inulin (100%) to yield a reactionmixture pH in the range of from 8 to 12, measured at the reactionmixture temperature (60° C. to 90° C.). The reaction is continued at thereaction temperature, after all the reagents have been added, for aperiod up to 90 minutes. The carboxyalkylinulin is subsequentlyrecovered in a manner known per sé.

The inventive method proceeds smoothly and gradually, while maintaininga controllably low viscosity during the total reaction, particularly inthe presence of high levels of inulin, and therefore substantiallyimproves and facilitates the course of the reaction and the yield of thereaction product.

The prior art relating to carboxyalkylinulins as such and methods forthe manufacture thereof is fairly substantial and diverse.Carboxymethylinulin salts have been known for a long time, see e.g.Czech patent No 90980 of 1958/1959. EP 0.733.073 describes a method forthe manufacture of carboxymethylinulin by reacting, under alkalineconditions, inulin and sodiumchloroacetate. The technology is, interalia, subject to substantial viscosity difficulties which can lead tolow conversions and undesirable by-products. Chien, J. Immunol. Methods26 (1979) 39-46, pertains to the preparation of carboxymethylinulin(CMI) thereby using a six-fold molar excess of sodium chloroacetate indilute alkaline solution at relatively low temperature. The CMI soprepared has a very low degree of substitution and the method iscumbersome and not suitable for any economically viable undertaking.Known CMI manufacturing technologies are known to be economicallydeficient and cannot be utilized for preparing carboxyalkylinulins withacceptable yields, purities and degrees of conversion. viscosity, inparticular gelling, problems constitute a major obstacle towardssecuring an acceptable manufacturing method.

It is therefore a major object of this invention to provide a method forpreparing carboxyalkylinulins with acceptable yields, purity and degreesof conversion having a degree of substitution (DS) above about 1.5 up toabout 3. It is another object of this invention to provide acarboxyalkylinulin manufacturing method which, while being conducted inthe presence of high levels of inulin reactant, is not subject toviscosity, in particular gelling, problems, which are known to diminishthe reaction completeness, and can lead to the formation of undesirableby-products and usually deliver reduced yields of the carboxyalkylinulinreaction product. The foregoing and other objects can now be achievedwith the aid of a narrowly-defined multi-step method arrangement.

The present invention resides in the discovery that carboxyalkylinulinscan be manufactured under alkaline conditions characterized in that:

(a) from 25 to 150 molar-%, expressed in relation to the molar amount ofmonosaccharide units in the inulin (100%), of anX-halogenoalkylcarboxylate, wherein the halogen is selected fromchlorine, bromine and iodine, the alkyl chain contains from 1 to 5carbon atoms, and X is an alkaline ion from the group of sodium andpotassium, is dispersed into an aqueous medium;

(b) adding to and dispersing into the halogenoalkylcarboxylate medium(a) the inulin to yield a slurry, having a pH, measured on the slurry ata temperature of from 20° C. to 70° C., in the range of from about 5 to8, containing from about 25% to about 70% by weight of the inulin,expressed in relation to the amount of water (100%) in the slurry;

(c) heating the slurry (b) to a temperature from about 60° C. to 90° C.followed by concurrently adding additional halogenoalkylcarboxylate, toyield a molar ratio of halogenoalkylcarboxylate:inulin of from 1.0 to5.0, and an alkaline hydroxide, from the group of sodium and potassiumhydroxide, in a quantity equimolar to the total level ofhalogenoalkylcarboxylate, plus an additional amount of the alkalinehydroxide of from 10 to 50 molar-%, expressed in relation to the molaramount of monosaccharide units in the inulin (100%), to yield a reactionmixture pH in the range of from 8 to 12, measured at the reactionmixture temperature (60° C. to 90° C.);

(d) continuing the reaction, after all the reagents have been added, fora period up to about 90 minutes, at the reaction temperature; and

(e) recovering the carboxyalkylinulin in a manner known per sé.

In preferred aspects herein, the molar ratio of halogenoalkylcarboxylate: inulin is in the range of from 1.5 to 4.5, and the reaction iscontinued for a period of 20 to 60 minutes after all the ingredientshave been added. The alkyl moiety, in the carboxyalkylinulin, ispreferably represented by a chain having from 1 to 3 carbon atoms, mostpreferably methyl.

The term “%” or “percent” as used throughout the application means,unless defined differently, “% by-weight” or “percent by-weight”. Theterms “fructan” and “inulin” are, unless specifically stateddifferently, used interchangeably. The terms “dispersion” and “solution”are used interchangeably

and represent, as one can appreciate, usually mixeddispersions/solutions or possibly individual solutions or dispersions.

The claimed invention concerns a method for the manufacture ofcarboxyalkylinulin. The alkyl moiety is generally represented by a chainhaving from 1 to 5, more preferably from 1 to 3 carbon atoms, mostpreferably methyl.

A reaction medium (a) is prepared by dispersing from 25 to 150,preferably from 70 to 100 molar-%, expressed in relation to the molaramount of monosaccharide units in the inulin (100%) of anX-halogenoalkylcarboxylate, wherein the halogen is selected fromchlorine, bromine and iodine, the alkyl contains from 1 to 5 carbonatoms, and X is an alkaline ion from the group of sodium and potassium,into an aqueous medium followed by adding to and dispersing into thecarboxylate medium of step (a) the inulin to yield a slurry having a pH,measured on the slurry at a temperature of from 20° C. to 70° C., in therange of from 5 to 8, preferably 6 to 8, containing from about 25 toabout 70, preferably from about 40 to 60% of the inulin, expressed inrelation to the amount of water (100%) in the slurry.

Fructans are oligo- and polysaccharides, which have a majority ofanhydrofructose units. The fructans can have a polydisperse chain lengthdistribution and can be straight- or branched-chain. Preferably, thefructan contains mainly β-2,1 bonds. The fructans can be productsobtained directly from a vegetable source or other sources and productsin which the average chain length has been modified, increased

or reduced, by fractionation, enzymatic synthesis or hydrolysis. Thefructans have an average chain length (degree of polymerization; DP) ofat least 3 to about 1000. Preferably the average chain length is from 3to 60, in particular from 5 to 30 monosaccharide units. Preferred inulinfor use is represented by β-2,1-fructan or a modified inulin. Modifiedfructans, suitable for use within the claimed technology, can berepresented by inulins with enzymatically increased chain length,fructan hydrolysis products having shortened chains and fractionatedproducts having a modified chain length. Fractionation of inulins can beachieved, for example, by means of known technologies including lowtemperature crystallization (see WO 94/01849), column chromatography(see WO 94/12541), membrane filtration (see EP-A-0440074, EP-A-0627490)or selective precipitation with alcohol. Hydrolysis to yield shorterfructans can be carried out, for example, enzymatically (endo-insulase),chemically (water and acid) or by heterogeneous catalysis (acidion-exchange resins). Reduced, oxidized, hydroxyalkylated and/orcross-linked fructans can also represent suitable starting materials.

The aqueous medium, into which the X-halogenoalkylcarboxylate isdispersed in step (a), can be represented by water or by an aqueousdispersion containing up to 35% , in one preferred execution from about10% to about 30% of the inulin (expressed in relation to the aqueousmedium). The use of aqueous inulin solutions as the aqueous medium instep (a) can be in order depending upon the inulin starting material,which can conveniently be made available as a solution.

The slurry (b) is subsequently heated to a temperature in the range offrom about 60° C. to about 90° C., preferably from about 60° C. to about70° C., followed by substantially concurrently adding additionalhalogenoalkylcarboxylate to yield a molar ratio ofhalogenoalkylcarboxylate:inulin of from 1.0 to 5.0, preferably of from1.5 to 4.5, and an alkaline hydroxide, from the group of sodium andpotassium hydroxide, in a quantity equimolar to the total level ofhalogenoalkylcarboxylate, plus an additional amount of the alkalinehydroxide in an amount of from 10 to 50 molar-%, expressed in relationto the molar amount (100%) of monosaccharide units in the inulin, tothus yield a reaction mixture pH in the range of from about 8 to 12,preferably from about 9.5 to 11.5 measured at the reaction temperature(60° C. to 90° C.).

The reaction is continued, at the reaction temperature, after all thereactants/ingredients have been added (c), for a period up to 90minutes, preferably of from 30 to 60 minutes.

The pH, in step (b) measured on the slurry at a temperature of from 20°C. to 70° C., is in the range of from 5 to 8, preferably 6 to 8 defines,within the context of the claimed method arrangement, since undesiredinulin degradation can occur at a pH lower than 5 and hydrolysis of thehalogenoalkylcarboxylate can occur at a pH greater than 8.

The carboxyalkylinulin reaction product can be recovered, as such orpurified, with the aid of conventional methods well known in this domainof the technology. Suitable examples of such purification methodsinclude nanofiltration.

The following Examples illustrate the invention and demonstrate thebenefits attached to the claimed method arrangement.

EXAMPLE 1

Inulin (500 g) was dispersed into a stirred solution of sodiummonochloroacetate (SMCA, 360 g) in water (500 g). This dispersion wasunder stirring gradually warmed to 70° C. The viscosity was measured atvarious temperatures thereby using a Brookfield , probe LV2, 60 rpm. Acomparative experiment was carried out by adding inulin (500 g) to water(500 g). The comparative viscosity measurements were as follows.Temperature (° C.) Example η Comparative η 20 533 paste 30 288 paste 40154 more than 16000 50 101 10000 60 85 4000 70 64 1000Viscosity measurements in: mPa/s.

These data show the reaction-friendly virtually-constant viscosity inaccordance with the invention versus the formation of kneadable reactionmixtures which yield very-low generally unacceptable conversion rates.

EXAMPLE 2

Inulin (150 g) was added to a stirred solution of SMCA (100 g) in water(200 g) at room temperature. The resulting slurry was then heated to 70°C. An aqueous solution of sodium hydroxide (50%, 215 g) and SMCA (200 g)were gradually added to the reaction mixture having a temperature of 70°C. The reaction was, after all the reagents were added, continued at thereaction temperature for a period of 90 minutes. Carboxymethylinulin (DS1.9, 765 g, 29% active salt) was formed with a yield of 75% .

EXAMPLE 3

Inulin (150 g) was added to a stirred solution of SMCA (80 g) in water(112 g) at room temperature. The resulting slurry was then heated to 75°C. An aqueous solution of sodium hydroxide (50%, 306 g) and SMCA (347 g)was gradually added to the inulin slurry having a temperature of 75° C.The reaction was, after all the reagents were added, continued at thereaction temperature for a period of 90 minutes.

Carboxymethylinulin (DS 2.5; 838 g; 34% active salt) was formed with ayield of 66% .

EXAMPLE 4

SMCA (300 g) was added, under stirring, to a slurry (650 g) containing30 wt-% inulin at 60° C. Inulin powder (360 g) was thereafter added tothe inulin slurry until an inulin concentration of 55%, with respect tothe amount of water in the slurry, was reached. The reaction mixture wasthen heated to 80° C. and one equivalent of sodium hydroxide (200 g, 50%aqueous solution), with respect to the amount of SMCA in the reactionmixture, was added while maintaining the reaction temperature at 80° C.Then SMCA (425 g) was added together with aqueous sodium hydroxide (50%,336 g). The reaction was, after all the reagents were added, continuedat the reaction temperature for a period of 90 minutes.Carboxymethylinulin (DS 1.46, 2270 g, 37% active salt) was formed with ayield of 81%.

1. A method for the manufacture of carboxyalkylinulin by reacting inulinwith monochlorocarboxylic acid under alkaline conditions, characterizedin that: (a) from 25 to 150 molar-%, expressed in relation to the molaramount of monosaccharide units in the inulin (100%), of theX-halogenoalkylcarboxylate, wherein the halogen is selected fromchlorine, bromine and iodine, the alkyl chain contains from 1 to 5carbon atoms, and X is an alkaline ion from the group of sodium andpotassium, is dispersed into an aqueous medium; (b) adding to anddispersing into the halogenocarboxylate medium (a) the inulin to yield aslurry, having a pH, measured on the slurry at a temperature of from 20°C. to 70° C., in the range of from about 5 to 8, containing from about25% to about 70% by weight of the inulin, expressed in relation to theamount of water (100%-by weight) in the slurry; (c) heating the slurry(b) to a temperature from about 60° C. to about 90° C., followed byconcurrently adding additional halogenoalkylcarboxylate, to yield amolar ratio of halogenoalkylcarboxylate : inulin of from 1.0 to 5.0, andan alkaline hydroxide, from the group of sodium and potassium hydroxide,in a quantity equimolar to the total level of halogenoalkylcarboxylate,plus an additional amount of the alkaline hydroxide of from 10 to 50molar-%, expressed in relation to the molar amount of fructose units inthe inulin (100%), to yield a reaction mixture pH in the range of from 8to 12, measured at the reaction temperature (60° C. to 90° C.); (d)continuing the reaction, after all the reagents have been added, for aperiod up to 90 minutes, at the reaction temperature; and (e) recoveringthe carboxyalkylinulin reaction product in a manner known per se.
 2. Themethod in accordance with claim 1 wherein the halogenoalkylcarboxylatein step (a) represents from 70% to 100 molar-% and wherein the slurry(b) contains from 40% to 60% by weight of inulin.
 3. The method inaccordance with claim 1 wherein the molar ratio ofhalogenoalkylcarboxylate:inulin is in the range of from 1.5 to 4.5. 4.The method in accordance with claim 1 wherein the slurry (b) is heatedto a temperature in the range of from 70° C. to 90° C.
 5. The method inaccordance with claim 4 wherein the pH of the reaction mixture is in therange of from 9.5 to 11.5.
 6. The method in accordance with claim 4wherein the reaction is continued for a period of from 20 to 60 minutesafter all the reagents have been added.
 7. The method in accordance withclaim 1 wherein the alkyl moiety in the carboxyalkylinulin isrepresented by a carbon chain having from 1 to 3 carbon atoms.
 8. Themethod in accordance claim 1 wherein the slurry (b) is heated to atemperature in the range of from 75° C. to 85° C.
 9. The method inaccordance with claim 1 wherein the carboxyalkylinulin iscarboxymethylinulin.
 10. The method in accordance with claim 1 whereinthe aqueous medium in step (a) contains optionally up to 35%-by weightof the inulin.
 11. The method in accordance with claim 10 wherein theaqueous medium in step (a) contains from about 10% to about 30%-byweight of the inulin.